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Chemicals of Abuse Sean Koon, MD California Academy of Family Physicians California Society of Addiction Medicine April 14, 2005 Substances Stimulants Cannabis Hallucinogens Opiates “Club” Drugs Stimulants Used for: “High” Energy, increase job performance, driving, studying Sexual enhancement Weight loss Cocaine Made from coca plant/leaf “chewed” in the Andes mountains of South America Original Coca-cola contained cocaine and kola beans Proposed by Freud for treatment of mental illness. He also used this habitually, finally conceding its detrimental effects in his last paper on the subject Forms of Use Cocaine HCL: snorted, not potent when smoked Freebase cocaine: converted to a base by removal of HCL with ether or NH4OH. Can be smoked or vaporized. More pure than reg. cocaine. Crack Cocaine: a form of freebase. Many impurities. Cheaper Cocaine Intoxication Effects: euphoria, confidence, decreased inhibitions 1. Rush (1-5 minutes) 2. High (10-20 minutes) 3. Crash 4. (Binge / cycle) Clinical Presenting Symptoms Chest pain Insomnia, fatigue Weight loss More Common Paranoia Nasal infections Headaches Sexual Dysfunction Magnon’s Syndrome (coke bugs) “Coke bugs” Medical Sequelae: Cocaine Can cause vasoconstriction or ischemia in various organs Cardiac Cocaine is the leading cause of drug related ER visits, excluding alcohol Risk of heart attack is increased 2x in the first 60 minutes of ingestion The amount of cocaine causing heart failure or dysfunction can vary widely Tachyarrythmias (v-tach/v-fib) LVH, abnormal segmental wall motion Medical Sequelae, cont’d ENT: Chronic rhinitis, perf. septum Neurologic: Seizures with acute intoxication (not withdrawal) CVA, TIA, SAH Pulmonary (rare): infarction, alveolar hemorrhage, pneumothorax GI: ischemia, ulcers (most in greater curvature or near pylorus) Cocaine and ETOH Cocaine + alcohol = cocaethylene Enhances the cardiac side effects (MI, arrythmias, cardiomyopathy) Combination increases the risk of sudden death 25X Amphetamines Originally marketed for asthma in 1932 as “benzedrine” used during WWII by Japan, US, Germany, Great Britain (200 million tablets supplied to American troops) Taken in pill form, snorted, smoked, injected Amphetamines Similar effect to cocaine, but longer lasting and cheaper Made from industrial reagents, over 150 methods of “cooking” Environmental impact: lots of toxic waste in the production Amphetamine Intoxication Alertness, energy, decreased inhibition, euphoria, increased confidence, increased sexual activity Confusion, dry mouth, anxiety, HTN, sensitivity to light and sound, bruxism Cardiac and neurological sequelae are similar to cocaine Does not work synergistically with alcohol like cocaine Amphetamine Intoxication 1. Rush (5-30 min) 2. High (4-16 hours) 3. Binge (3-15 days) 4.“Tweaking”(24 hours) End of high dose binge: depression, irritability, w/paranoia aggression 5. Crash (1-3 days of extreme fatigue/sleep) Compare with cocaine 1. Rush (1-5 minutes) 2. High (10-20 minutes) Medical Sequelae Psychosis, delusions, hallucinations, violence, formication “speed bugs, crank bugs”, stereotypy Decay and discoloration of teeth Seizures (with intoxication only) Withdrawal usually requires no medical management (symptomatic) Marijuana Used throughout history for rope, clothing, food and oil (from seeds) Earliest written reference: Chinese Emperor Shen Nung in 2737 recommended for gout, constipation and rheumatism Marijuana, cont’d Found to work on CB1 (in the brain) and CB2 (in the spleen, on macrophages) receptors “anandamide” is endogenous ligand that binds to these receptors. Affects memory consolidation d/t effect on hippocampus Via the amygdala, MJ interacts with: novelty, appetite regulation, pain threshold regulation, anxiety and fear regulation Marijuana Intoxication Peak high 15-45 minutes Acceleration of HR for 10-30 minutes (by 30- 50%), moderate increase in BP Poor judgment and motor coordination (for 4-8 hours even after the “high” is gone Very significant risk in driving Redding of the eyes Slight drop in body temp. Dryness of mouth and throat, possible blistering MJ Intoxication Desired effects Euphoria Relaxation, reduced physical activity Rapid mood changes, heightening of humor Intensifies ordinary experiences Other effects Anxiety or panic Impaired memory, esp. short term Reduced concentration MJ: Consequences Over the years many medical consequences were suggested but only the lung consequences are consistently found in the research: Bronchitis Emphysema Lung Cancer Many biopsychosocial issues: relationships, education, anhedonia and mood problems, legal Can serve as a “gateway drug” (3x more likely to lead to dependency if smoked before 18 years old) MJ: Medical Applications Medical applications: Antiemetic Pain management (esp. neuropathic and inflammatory pain in cancer patients) Asthma Glaucoma Appetite stimulant Hallucinogens: LSD POTENT: One ounce=567,000 hits Taken on blotter paper, gels, or sugar cubes Effect in 30-60 minutes. May last for up to 12 hours It’s believed that as few as 10 people make all of the LSD used in the US! LSD cont’d Perceptual distortion, impaired judgement Synesthesia: “crossing of senses” Dilated pupils, increased saliva, increase HR, BP, RR Sometimes extreme fear, anxiety and paranoia with high risk of physical injury: “talk down” Flashbacks can be weeks months, or years after last use No evidence of physical addiction PCP “Dissociative anaesthetic” Introduced by Parke-davis (1967) for anesthetizing large animals Usually smoked (“sherms”), sometimes snorted or swallowed Highly variable concentrations PCP Intoxication Onset 2-5 minutes Peak 15-30 minutes Lasts 4-6 hours Fat soluble: sporadic Three levels of intoxication concentrations Low dose: “drunken state” Mod. dose: agitation, hallucinations, muscle rigidity, poor coordination, marked nystagmus Big dose: convulsions, respiratory depression, cardiac instability, coma Possible agitation in withdrawal, 11-15 hrs after last dose “Flashbacks” (true chemical) PCP: Medical Sequelae Rhabdomyolysis Renal failure Intractable seizures Hyperthermia HTN, CVA Psychosis Opiates: Heroin Desired effect: euphoria Respiratory depression – Sometimes a purchase has greater purity than expected Nearly all heroin OD’s secondary to this Often combined with cocaine to make “speedballs” Most medical complications are due to injection use Heavy risks of the “Heroin lifestyle” Heroin Withdrawal Usually peaks in 24-72 hours, gone by 7-10 days, usual detox is 3-7 days Dilated pupils Goosebumps Nausea, Vomiting, Diarrhea Increased BP, HR Muscle pain/spasms Rhinorrhea, watery eyes Yawning (More on withdrawal in Dr. Ey’s lecture) Medical Concerns with Injection Drug Users Hepatitis, especially Hepatitis C Transmitted by blood: needles, syringes, cottons, cookers, rinsewater Studies claim 70+% Heroin users are Hep C+ Infective endocarditis, typically right sided, 50% staph, 15% strep Pneumonia concomitant cigarettes, malnutrition, depressed gag reflex More often H. flu, S. aureus, Ps. aeruginosa relative to nonIDUs IDU’s have increased risk of TB activation, unknown why Cellulitis, abscesses (mostly staph, often strep) HIV Medical Issues with Injected Drugs, cont’d Necrotizing fasciitis Pain way out of proportion to findings Medical emergency Renal: Nephrotic syndrome Glomerulonephritis (usually from to bacterial endocarditis) Notable RX opiates: Meperidine, Propoxyphene, and Pentazocine (and tramadol the partial agonist) Can all cause seizures in OD as well as with higher therapeutic doses May cause agitation, confusion, and frank delirium when given around the clock Long acting opiates Oxycontin attractive to addicts for its high amount of oxycodone. Crushed form can be injected or snorted (ms contin abused as well, but apparently not as easy to crush/snort/inject) Duragesic patches can be chewed or squeezed and contents injected Club Drugs Used typically by teens/youth GHB (Gamma Hydroxybutyric acid) Liquid, dosed in “capfuls” Rapid onset, ½ life 20 minutes Side effects Dizzines, nausea, emesis, dec. resp, coma Overdose similar to sedatives, consciousness returns within 5 hours after ingestion Club Drugs Ketamine Similar to PCP SE’s confusion, delirium, psychosis, coma,seizures DMX (dextromethorphan): euphoria, dissociation, hallucinosis May last 3-6 hours Doses up to 100x therapeutic dose (esp. “Coricidin HBP”) Club Drugs: Ecstasy/MDMA Desired effects: Stimulant/psychedelic Altered time perception Decreased aggression/sexual activity Empathy, Enhanced touch Light trailers MDMA Intoxication Intox. 30-45 minutes after ingestion Intense effects 60-90 minutes after ingestion Most effects wear off by 4-6 hours Some effects may persist for days to longer MDMA: Adverse effects Causes large amounts of serotonin to be released, and prevents re-uptake Serotonin syndrome (elevated body temp., sweating, spasm, coma, CV collapse, etc.) Heat stroke Fluid & electrolyte imbalances Anxiety, confusion, sleep disturbance, paranoia Muscle tension, bruxism Depression, perhaps even chronic depression after few doses (after w/d of drug) Sedatives Interact with GABA Receptor Cross-tolerant with alcohol, thus useful for withdrawal Benzodiazepines Barbiturates SOMA : metabolizes to meprobamate, a barbiturate-like compound Withdrawal may mimic the indication (e.g. anxiety or insomnia) Seizures and delirium are possible in withdrawal from sedatives Questions… Primary Care Workshop California Academy of Family Physicians and California Society of Addiction Medicine April 14, 2005